BJMG 16/1 (2013) 13-20
10.2478/bjmg-2013-0013
ORIGINAL ARTICLE
HUMAN RING CHROMOSOMES – NEW INSIGHTS
FOR THEIR CLINICAL SIGNIFICANCE
Guilherme RS1,2, Klein E1, Hamid AB1, Bhatt S1, Volleth M3, Polityko A4, Kulpanovich
A5, Dufke A6, Albrecht B7, Morlot S8, Brecevic L9, Petersen MB10, Manolakos E10,
Kosyakova N1, Liehr T1*
*Corresponding Author: Dr. Thomas Liehr, Institut für Humangenetik, Kollegiengasse 10, Postfach D-07740
Jena, Germany; Tel.: +49-3641-935533; Fax: +49-3641-935582; E-mail: [email protected]
ABSTRACT
Twenty-nine as yet unreported ring chromosomes were characterized in detail by cytogenetic
and molecular techniques. For FISH (fluorescence
in situ hybridization) previously published high
resolution approaches such as multicolor banding
(MCB), subcentromere-specific multi-color-FISH
(cenM-FISH) and two to three-color-FISH applying
locus-specific probes were used. Overall, ring chromosome derived from chromosomes 4 (one case),
10 (one case), 13 (five cases), 14, (three cases), 18
(two cases), 21 (eight cases), 22 (three cases), X (five
cases) and Y (one case) were studied. Eight cases
were detected prenatally, eight due developmental
delay and dysmorphic signs, and nine in connection
Jena University Hospital, Friedrich Schiller University, Institute of
Human Genetics, D-07743 Jena, Germany
2
Department of Morphology and Genetics, Universidade Federal de
São Paulo, 04023-900 São Paulo, SP, Brazil
3
Institut für Humangenetik, Otto-von-Guericke-Universität Magde­
burg, 39120 Magdeburg, Germany
4
National Medical Center, ‘Mother and Child’, 220053 Minsk, Belarus
5
Belarus State Medical University, 220116 Minsk, Belarus
6
Institut für Humangenetik, 72076 Tübingen, Germany
7
Institut f. Humangenetik, Universitätsklinikum Essen, 45122 Essen,
Germany
8
MVZ WagnerStibbe, 30159 Hannover, Germany
9
School of Medicine Zagreb University, Croatian Institute for Brain
Re­search, 1000 Zagreb, Croatia
10
Eurogenetica S.A., 11527 Ampelokipoi, Athens, Greece
1
with infertility and/or Turner syndrome. In general,
this report together with data from the literature, supports the idea that ring chromosome patients fall into
two groups: group one with (severe) clinical signs
and symptoms due to the ring chromosome and group
two with no obvious clinical problems apart from
infertility.
Keywords: Ring chromosomes; Fluorescence
in situ hybridization (FISH); Genotype-phenotype
correlations.
INTRODUCTION
It is common sense that ring chromosomes result from two terminal breaks on both chromosome
arms followed by fusion of the broken ends, leading
to the loss of genetic material. Alternatively, they
can be formed by telomere-telomere fusion without
deletion [1] or the so-called McClintock mechanism
[2]. Also more complex mechanisms of ring chromosome formation have been proposed [3,4]. Ring
chromosomes are also observed as small supernumerary marker chromosomes (sSMC) [5,6], however, their formation seems to be completely different from that of ring chromosomes in a numerically
normal karyotype [7,8].
Phenotypes associated with ring chromosomes
can be highly variable, since in addition to the primary deletion associated with ring formation, secondary loss or gain of material may occur due to
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HUMAN RING CHROMOSOMES
ring chromosome instability. It has also been reported that the phenotype of ring chromosome patients
can overlap that of the deletion of both ends of the
respective chromosome syndromes without ring
formation. Moreover, there have also been numerous reports on ring chromosomes without clinical
consequences, apart from possible infertility, if no
relevant genetic material was lost due to ring chromosome formation [1]. Here we report ring chromosomes observed in 29 patients with (severe) clinical problems, and/or solely infertility, evaluated by
cytogenetic and molecular techniques.
MATERIALS AND METHODS
Twenty-nine cases with ring chromosomes were
studied for different clinical reasons (see Table 1).
Eight cases were detected prenatally (amniocytes
studied), eight due developmental delay and dysmorphic signs, and nine in connection with infertility and/or Turner syndrome; in four cases the reason
for the study was not transmitted to the laboratory
at Jena, Germany (peripheral blood studied). Chromosomes were prepared according to standard procedures. The cases were studied using standard banding cytogenetics and by means of FISH (fluorescence
in situ hybridization). Previously published high
resolution approaches such as multicolor banding
(MCB) [9,10], subcentromere-specific multico­lorFISH (cenM-FISH) [6] and two to three-color-FISH
applying locus-specific and/or commercially available centromere specific probes (Abbott/Vysis, Wiesbaden, Germany and/or Kreatech, Amsterdam, The
Netherlands) were used. Locus-specific probes and
also commercial probes, such as subtelomeric ones
(Abbott/Vysis) or bacterial artificial chromosome
Table 1. Details on the 29 studied ring chromosome cases according to their chromosomal origin, karyotype,
age at diagnosis and clinical signs. [DD: developmental delay; DS: dysmorphic signs; IUGR: intrauterine growth
retardation; NA: not available; TOP: termination of pregnancy; y = year(s)]
Case Chromosome
#
of Origin
Karyotype
R-1
4
46,XX,r(4)(p16.2q34.1)[14]/
46,XX,r(4)(::p11->q32.1::q32.1->p11::)[4]/
46,XX,r(4)(p11q35.1)[3]/
45,XX,-4[3]/
46,XX,r(4)(::p16.2->q35.1::q12->q35.1::)[2]/
46,XX,r(4)(::p16.2->q27::q11->q32.1::)[2]/
47,XX,r(4)(::p16.2->q35.1::q12->q35.1::),+r(4)(p11q35.1)[1]/
47,XX,-4,+r(4)(::p16.2->q27::q11->q32.1::)x2[1]/
47,XX,-4,+r(4)(::p11->q32.1::q32.1->p11::)x2[1]/
47,XX,-4,r(4)(::p16.2->q34.1::)x2[1]/
46,XX,r(4)(::p16.2->q34.1::p16.2->q34.1::)[1]/
46,XX,r(4)(p16.2q35.1)[1]/
45,XX,-4,-14,+der(4)t(4;14)(q32.1;q11.2)[1]
R-2
10
47,XY,del(10)(q10q25.3),+r(10)(q10q25.3)[23]/
46,XY,del(10)(q10q25.3)[6]/
47,XY,del(10)(q10q25.3),+r(10)(::q10->q25.3::q10->q25.3::)[1]
R-3
13
46,XY,r(13)(p11.2q33.3~34)[9]/
46,XY,r(13)(::p11.2q33.3~34::p11.2q33.3~34::)[1]
R-4
13
46,XX,r(13)(p11.1q33.3)[13]/
46,XX,r(13,13)(::p11.1->q33.3::p11.1->q33.3::)[1]/
45,XX,-13[1]
R-5
13
46,XX,r(13)(p11q32.3)[93%]/
46,XX,r(13)(::p11->q32.3::p11->q32.2::)[7%]
R-6
13
45,XX,-13[50]/
46,XX,r(13)(p11.1q33~34)[50]
R-7
13
46,XY,r(13)(p1?2q34)
R-8
14
46,XX,r(14)(::p12->q32.2::q32.2->q23::)[20]/
46,XX,r(14)(p12q32.2)[4]/
46,XX,del(14)(q21)[1]/
46,XX[1]
Age at
Diagnosis
5 years
Clinical
Signs
DD
DS
5 years
DD
DS
prenatal
IUGR, DS
TOP
DD, DS
microcephaly
dwarfism
DD
DS
IUGR
TOP
NA
DD
DS
6 years
adult
prenatal
NA
newborn
Continue
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BALKAN JOURNAL OF MEDICAL GENETICS
Guilherme RS, Klein E, Hamid AB, Bhatt S, Volleth M, Polityko A, Kulpanovich A, Dufke A,
Albrecht B, Morlot S, Brecevic L, Petersen MB, Manolakos E, Kosyakova N, Liehr T
Table 1. Continued
Case Chromosome
#
of Origin
R-9
14
46,XY,r(14)(p13q32.2)[82]/
45,XY,-14[18]
R-10
14
46,XX,r(14)(p1?3q24.3)
R-11
18
R-12
18
R-13
21
R-14
21
R-15
21
R-16
21
R-17
21
R-18
21
R-19
21
R-20
21
R-21
R-22
R-23
22
22
22
R-24
X
R-25
X
R-26
X
R-27
X
R-28
X
R-29
Y
Karyotype
46,XX,r(18)(p11.1q12.3~21.1)[7]/
der(18)(:p11.1->q12.3~21.1:)[12]
46,XX,r(18)(p11.21q23)[7]/
45,XX,-18[3]
45,XX,-21[50%]/
46,XX,r(21)(p12q22.3)[30%]/
46,XX,del(21)(q22.3)[20%]
46,XX,r(21)(p1?3q22.1)[64]/
45,XX,-21[26]/
46,XX[10]
46,XY,r(21)(::p11->q22::p11q22::)[10]/
46,XY,r(21)(::p11->q22::)[7]/
45,XY,-21[7]/
46,XY,der(21)(:p11->q22::p11->q22:)[2]/
46,XY,der(21)(:p11->q22:)[1]/
46,XY,r(21)(::p11->q22::p11q2?1::)[1]/
46,XY,der(21)(:q22->p11::p11->q22:)[1]/
47,XY,r(21)(::p11->q22::),+r(21,21)(::p11->q22::p11q22::)[1]
46,XY,r(21)(p12q22.3)[23]/
46,XY,r(21;21)(::p12->q22.3::p12->q22.3::)[4]/
45,XY,-21[2]/
46,XY,r(21)(p12q21)[1]
46,XY,r(21)(p1?2q22.3)[21]/
46,XY,del(21)(:p1?2->q22.3:)[13]/
46,XY,r(21)(::p1?2->q22.3::q22.3->p1?2::p1?2->q22.3::q22.3->p1?2::)[1]
46,XY,r(21)(p11.1q22.?2)[9]/
46,XY,r(21;21)(::p11.1->q22.?2::p11.1->q22.?2::)[1]
46,XN,der(21)(:q11.2->p11.1~11.2::p11.1~11.2->q22.3:)[8]/
46,XN,del(21)(:p11.1~11.2->q22.3:)[7]/
46,XN,r(21)(::p11.1~11.2->q22.3::)[4]/
45,XN,-21[1]
46,XX,r(21)(::p11.2->q22.3::)[33]/
46,XX,r(21)(::p11.2->q22.3::p11.2->q22.3::)[5]/
47,XX,r(21)(::p11.2->q22.3::),+del(21)(p11.2:)[1]/
46,XX[1]
46,XN,r(22)(p1?2q1?3)
46,XY,r(22)(p11q13.3)
46,XX,r(22)(::p12->q11.1::p11.1->q11.1::q11.1->p12::)[3]/
46,XX,der(22)(:q11.1->p12::p12->q11.1:)[2]/
46,XX,r(22)(::p12>q11.1::)[2]/
46,XX,r(22)(::p11.1->q11.1::p11.1->q11.1::)[1]
45,X[56]/
46,X,r(X)(p11.1q24)[44]
45,X[19]/
46,X,r(X)(p11.2q13.?1)[11]
45,X[46]/
46,X,r(X)(p11.?22q13.3)[4]/
47,X,r(X)(p11.?22q13.3)x2[1]
45,X[17]/
46,X,r(X)(p11.23q28)[7]
45,X[70%]/
46,X,r(X)(p22.1~22.2->q21.1)[27%]/
46,X,r(X)(::p22.1~22.2->q21.1::q21.1->p22.1~22.2::)[2]/
47,X,-X,+r(X)(::p22.1~22.2->q21.1::q21.1->p22.1~22.2::)x2[1]
45,X[?%]/46,X,r(Y)(::p11.3->q11.2?3::q11.2?3->p11.3::)[?%]
Age at
Diagnosis
1 year
prenatal
prenatal
prenatal
11 years
Clinical
Signs
DD
DS
DS
TOP
NA
hydrocephalus
TOP
DD
DS
1 year
DD
DS
prenatal
DS
TOP
prenatal
NA
32 years
infertility
NA
NA
prenatal
NA
17 years
premature
ovarian
insufficiency
26 y
NA
NA
infertility
NA
NA
16 y
Turner syndrome
40 y
infertility
30 y
Turner syndrome
28 y
infertility
26 y
infertility
adult
infertility
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HUMAN RING CHROMOSOMES
(BAC) probes, were applied. Labeling and application of the probes was done according to the manufacturer’s instructions or as reported [11].
RESULTS AND DISCUSSION
In 29 cases with ring chromosomes, the chromosomal origin and content could be determined
using molecular cytogenetics. The rings were derived from chromosome 4 (one case), 10 (one case),
13 (five cases), 14, (three cases), 18 (two cases), 21
(eight cases), 22 (three cases), X (five cases) and Y
(one case). The exact breakpoints and mosaic states
are summarized in Table 1 and examples of the
FISH results are shown in Figure 1. In the following data, the obtained results were compared with
the literature by chromosomal origin; afterwards,
A
MCB13
the chromosomal imbalances were analyzed, and
finally, a conclusion was drawn.
Analyzed Rings by Chromosomal Origin.
Numerous cases for ring chromosomes 4 have been
reported previously [12-14]. Interestingly, those
cases fall into two cytogenetic groups: one group
where the ring is stable and the other group where it
is unstable within the studied cells, as in case R-1.
Further studies are necessary to rule out where this
instability comes from, and what the clinical impact
is. To the best of our knowledge, no clinically normal ring chromosome 4 case has yet been reported.
In case R-2, the first ever seen balanced ring formation involving chromosome 10 formed by the McClintock mechanism [2] is reported. The rearrangement was connected with clinical problems, as the
ring was lost in ~20.0% of the cells. Ring chromo-
B
cep 13/21
subtel 13qter
r(13)
r(13)
#13
R-7
#13
C
or
#21
r(21)
dr(21)
cep 13/21
RP11-89H21
in 21q11.2
subtel 21qter
or plus
der(21)
R-23
Figure 1. Representative results for the molecular cytogenetic characterization of the studied ring chromosomes.
A) In case R-7, a ring chromosome derived from chromosome 13 [r(13)] was present as well as a normal chromosome
13 (#13); breakpoints were characterized by MCB as 13p1?2 and 13q34. B) Application of a subtelomeric probe
for chromosome 13qter (subtel 13qter) together with a centromeric probe for chromosomes 13 and 21 (cep 13/21) confirmed
a partial deletion in 13qter. C) Application of a centromeric probe for chromosomes 13 and 21 (cep13/21) with a subtelomeric probe for chromosome 21qter (subtel 21qter) in combination with a subcentromeric probe in 21q11.2 revealed the
presence of three derivatives of a chromosome 21 in case R-23; a ring [r(21)], a double ring [dr(21)] and a shortened derivative of chromosome 21 [der(21)] were observed. For final karyotype results, see Table 1.
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BALKAN JOURNAL OF MEDICAL GENETICS
Guilherme RS, Klein E, Hamid AB, Bhatt S, Volleth M, Polityko A, Kulpanovich A, Dufke A,
Albrecht B, Morlot S, Brecevic L, Petersen MB, Manolakos E, Kosyakova N, Liehr T
somes derived from chromosome 10 are rare (only
about 10 cases) and were recently reviewed [15].
Martin et al. [16] suggested the existence of
a ring chromosome 13 syndrome and gave an incidence of 1/58,000 in live births. Here, five cases
with ring chromosomes 13 were studied (R-3 to R7),
all of them were clinically abnormal.
Similarly to chromosome 13 derived rings,
chromosome 14 is also suggested as a specific syndrome [17]. In concordance with the literature, all
three ring chromosome 14 cases studied here (R-8 to
R10) had an abnormal pheno-type.
Ring chromosomes 18 were present in the prenatally studied cases R-11 and R-12. Here too, a recognizable syndrome was suggested [18]. Similar to
chromosome 4, for rings derived from chromosome
18, cytogenetically stable (e.g., present two cases)
and unstable rings [19] are reported.
Eight cases with ring chromosomes 21 were
char-acterized in the present study (cases R-13 to
R-20). While cases R-13 to R-15 were unbalanced
and led to clinical signs, two of the cases just detected were due to infertility (R-17 and R-20). As
reported in [20], most, if not all ring chromosome 21
cases are mosaic, as the ones here described. A ring
chromosome 21 syndrome was also postulated [21].
The three ring chromosome 22 cases were either cyto-genetically stable (R-21 and R-22) or unstable (R-23). The reason for the cytogenetic study
was available only for case R-21; it was infertility,
and in the literature there are several similar cases
reported [22].
Turner syndrome is cytogenetically characterized by karyotype 45,X; in ~5.0% of the cases, this
main cell line is accompanied by a second one having 46 chromosomes due to an additional derivative
X- or Y-chromosome [23]. Here, six such cases were
characterized in more detail, as they had a ring derived from the X-chromosome (cases R-24 to R-28)
or the Y-chromosome (R-29). Interestingly, all cases were detected during adulthood and only two of
them due to a suspicion of Turner syndrome (R-24
and R-26). The majority of the cases were referred
due to infertility.
Ring Chromosome-Induced Imbalances. In
all 29 studied ring chromosome cases (Table 1), euchromatic imbalances were present except for cases
R-7, R-21 and R-22. In the latter, clinical data was
available only for case R-21, and infertility was the
only clinical problem observed there. Primarily, case
R-2 did not have any imbalance due to a ring chromosome, but double ring formation and loss of the
ring chromosome led to a partial tri - or monosomy
in 23.0% of the patient’s cells overall.
Imbalances were exclusively induced by the
ring chromosome formation in case R-10. Moreover,
in all the remaining 24 cases, imbalances were also
caused by sec-ondary effects of the ring chromosome
formation: i) double ring formation: R-1, R-3 to R-5,
R-8, R-15, R-16, R-18 to R-20, R-23, R-28 and
R-29; ii) ring doubling: R-1, R-15, R-26 and R-28;
iii) complex changes of the ring itself: R-1, R-15 to
R-17 and R-23; iv) ring opening (including further
rearrangements): R-1, R-8, R-11, R-13, R-15, R-17,
R-19, R-20 and R-23; v) loss of the ring: R-1, R-4,
R-6, R-8, R-9, R-12 to R-16, R-19 and R-24 to R-29.
Similar observations were also made for other
ring chromosomes 22. The idea that there might even
be a “ring syndrome” irrespective of the chromosomal origin of the ring [24] might be due to the gross imbalances induced by these secondary changes [25].
CONCLUSIONS
In general, this report supports the idea that ring
chro-mosome patients fall into two groups: a larger
one with (severe) clinical signs and symptoms due
to the ring chromosome and a smaller one with no
obvious clinical problems apart from infertility. The
latter can be due to gamete instability at meiosis due
to the ring chromosome which leads to an increased
breakdown [22]. This cytogenetic study of 29 rings
also shows that chromosomal imbalances are secondary inducings in ~85.0% of the cases by loss of
the ring (68.0%), double ring formation (52.0%),
ring opening (36.0%), ring doubling (16.0%) and
complex changes of the ring itself (16.0%).
ACKNOWLEDGMENTS
This study was supported in part by the DAAD
(D07/ 00070 and Ph.D. fellowship to ABH), BMBF/
DLR (BLR 10/006), Else Kröner-Fresenius-Stiftung
(2011_A42) and CAPES (Grant to RSG #2333-112). Single cases were provided from Germany by
Dr. Höls-Herpertz, Medizinische Genetik, Bensberg; Dr. Kunz, Humangenetische Apparategemeinschaft, Berlin; Dr. Belitz, Pränatale Diagnostic und
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HUMAN RING CHROMOSOMES
Medizinische Genetic, Berlin; Dr. Tönnies, Charité,
Berlin; Dr. Süss, Humangenetik, Cottbus; Dr. Junge,
Genetic, Dresden; Dr. Bartz, Genetic, Düsseldorf;
Dr. Zoll and Dr. Bartels, Institute für Humangenetik,
Göttingen; Dr. Kroisel, Institute für Humangenetik, Greifs-wald; Dr. Schulze, Humangenetik, Hannover; Dr. Ovens-Räder, Humangenetik, München;
Armenia: Dr. Mkrtchyan and Dr. Manveylan, Department of Genetics, Yerevan; Turkey: Dr. Ergun,
Department of Medical Genetics, Ankara.
REFERENCES
1. Guilherme RS, Meloni VF, Kim CA, Pellegrino
R, Takeno SS, Spinner NB, et al. Mechanisms
of ring chromosome formation; ring instability
and clinical consequences. BMC Med Genet.
2011; 12(1): 171.
2. Baldwin EL, May LF, Justice AN, Martin CL,
Led-better DH. Mechanisms and consequences
of small supernumerary marker chromosomes:
from Barbara McClintock to modern geneticcounseling issues. Am J Hum Genet. 2008;
82(2): 398-410.
3. Stankiewicz P, Brozek I, Helias-Rodzewicz Z,
Wierzba J, Pilch J, Bocian E, et al. Clinical and
molecular-cytogenetic studies in seven patients
with ring chromosome 18. Am J Med Genet.
2001; 101(3): 226-239.
4. Stavropoulou C, Mignon C, Delobel B, Moncla A, Depetris D, Croquette MF, et al. Severe
phenotype resulting from an active ring X chromosome in a female with a complex karyotype:
characterisation and replication study. J Med
Genet. 1998; 35(11): 932-938.
5. Liehr T. Small supernumerary marker chromosomes (http://www.fish.uniklinikum-jena.de/
sSMC.html [accessed 28/06/2012]).
6. Liehr T, Mrasek K, Weise A, Dufke A, Rodríguez L, Martínez Guardia N, et al. Small supernumerary marker chromosomes–progress
towards a genotype-phenotype correlation. Cytogenet Genome Res. 2006; 112(1-2): 23-34.
7. Tönnies H, Hennies HC, Spohr HL, Neitzel
H. Characterization of the first supernumerary
tricentric ring chromosome 1 mosaicism by
conventional and molecular cytogenetic techniques. Cytogenet Genome Res. 2003; 103 (12): 28-33.
8. Liehr T, Claussen U, Starke H. Small supernumerary marker chromosomes (sSMC) in humans. Cytogenet Genome Res. 2004; 107(1-2):
55-67.
9. Liehr T, Heller A, Starke H, Rubtsov N, Trifonov V, Mrasek K, et al. Microdissection
based high resolution multicolor banding for all
24 human chromosomes. Int J Mol Med. 2002;
9(4): 335-339.
10. Weise A, Mrasek K, Fickelscher I, Claussen U,
Cheung SW, Cai WW, et al. Molecular definition of high-resolution multicolor banding
probes: first within the human DNA sequence
anchored FISH banding probe set. J Histochem
Cytochem. 2008; 56(5): 487-493.
11. Liehr T, Weise A, Heller A, Starke H, Mrasek
K, Kuechler A, et al. Multicolor chromosome
banding (MCB) with YAC/BAC-based probes
and region-specific micro dissection DNA libraries. Cytogenet Genome Res. 2002; 97(1-2):
43-50.
12. Lurie IW. Further study of genetic interactions:
loss of short arm material in patients with ring
chromosome 4 changes developmental pattern
of del(4)(q33). Am J Med Genet. 1995; 56(3):
308-311.
13. Soysal Y, Balci S, Hekimler K, Liehr T, Ewers
E, Schoumans J, et al. Characterization of double ring chromosome 4 mosaicism associated
with bilateral hip dislocation; cortical dysgenesis; and epilepsy. Am J Med Genet A. 2009;
149A(12): 2782-2787.
14. Chen CP, Lin SP, Su YN, Chern SR, Tsai EJ,
Wu PC, et al. Mosaic ring chromosome 4 in
a child with mild dysmorphisms; congenital
heart defects and developmental delay. Genet
Couns. 2011; 22(3): 321-326.
15. Gunnarsson C, Graffmann B, Jonasson J. Chromosome r(10)(p15.3q26.12) in a newborn child:
case report. Mol Cytogenet. 2009; 2(1): 25.
16. Martin NJ, Harvey PJ, Pearn JH. The ring
chromosome 13 syndrome. Hum Genet. 1982;
61(1): 18-23.
17. Giovannini S, Frattini D, Scarano A, Fusco
C, Bertani G, Della Giustina E, et al. Partial
epilepsy complicated by convulsive and nonconvulsive episodes of status epilepticus in a
18
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BALKAN JOURNAL OF MEDICAL GENETICS
Guilherme RS, Klein E, Hamid AB, Bhatt S, Volleth M, Polityko A, Kulpanovich A, Dufke A,
Albrecht B, Morlot S, Brecevic L, Petersen MB, Manolakos E, Kosyakova N, Liehr T
patient with ring chromosome 14 syn-drome.
Epileptic Disord. 2010; 12(3): 222-227.
18. Ono T, Okuma M, Hamada T, Motohashi N,
Moriyama K. A case of ring chromosome 18
syndrome treated with a combinedorthodonticprosthodontic approach. Cleft Palate Craniofac
J. 2010; 47(2): 201-210.
19. Carreira IM, Mascarenhas A, Matoso E, Couceiro AB, Ramos L, Dufke A, et al. Three unusual but cytogenetically similar cases with up
to five different cell lines involving structural
and numerical abnormalities of chromosome
18. J Histochem Cytochem. 2007; 55(11): 11231128.
20. Chen CP, Lin YH, Chou SY, Su YN, Chern SR,
Chen YT, et al. Mosaic ring chromosome 21;
monosomy 21; and isodicentric ring chromosome 21: prenatal diagnosis; molecular cytogenetic characterization; and association with
2-Mb deletion of 21q21.1-q21.2 and 5-Mb deletion of 21q22.3. Taiwan J Obstet Gynecol.
2012; 51(1): 71-76.
21. Capaccio P, Clemente IA, Marchisio P, Selicorni A, Esposito S, Pignataro L. Videoendoscopic
rehabilitation of iatrogenous Stensen-ductacquired atresia in a patient with ring chromosome 21 syndrome and drooling. J Pediatr
Surg. 2008; 43(11): e17-e20.
22. Rajesh H, Freckmann ML, Chapman M. Azoospermia and paternal autosomal ring chromosomes: case report and literature review. Reprod Biomed. Online 2011; 23: 466-470.
23. Liehr T, Mrasek K, Hinreiner S, Reich D, Ewers E, Bartels I, et al. Small supernumerary
marker chromosomes (sSMC) in patients with
a 45;X/46;X;+mar karyotype – 17 new cases
and a review of the literature. Sex Dev. 2007;
1(6): 353-362.
24. Kosztolányi G. Does “ring syndrome” exist? An
analysis of 207 case reports on patients with a ring
auto-some. Hum Genet. 1987; 75(2): 174-179.
25. Cote GB, Katsantoni A, Deligeorgis D. The cytogenetic and clinical implications of a ring chromosome 2. Ann Genet. 1981; 24(4): 231-235.
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